US4739055A - Anhydrous, stable, crystalline δ-form of prazosin hydrochloride - Google Patents
Anhydrous, stable, crystalline δ-form of prazosin hydrochloride Download PDFInfo
- Publication number
- US4739055A US4739055A US06/660,871 US66087184A US4739055A US 4739055 A US4739055 A US 4739055A US 66087184 A US66087184 A US 66087184A US 4739055 A US4739055 A US 4739055A
- Authority
- US
- United States
- Prior art keywords
- prazosin hydrochloride
- crystalline
- stable
- anhydrous
- prazosin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the invention is related to a novel, anhydrous, stable, crystalline ⁇ -form of prazosin hydrochloride or 2-[4-(2-furoyl)-piperazin-1-yl]4-amino-6,7-dimethoxyquinazoline hydrochloride.
- the ⁇ -form is prepared by azeotropic distillation by aid of selected organic solvents.
- Prazosin hydrochloride is a well-known hypotensive agent of the following formula: ##STR1##
- the ⁇ -form is relatively non-hygroscopic and stable. Hence it is more advantageous for handling, storing and formulations than the other forms of prazosin hydrochloride.
- relatively non-hygroscopic as used in U.S. Pat. No. 4,092,315 (DE No. 2,708,192) means that a sample initially containing not more that about 0.5% water, when exposed to a temperature of about 37° C. and a relative humidity of about 75% for a period of about 30 days, contains not more than 1.5% water.
- U.S. Pat. No. 4,092,315 discloses a process for preparing an amorphous anhydrate of prazosin hydrochloride.
- the anhydrate is prepared by drying a sample of prazosin hydrochloride polyhydrate in a vacuum desiccator at 100° C. for 12-15 hours.
- the anhydrate thus prepared is amorphous containing about 1% of water.
- samples of the anhydrate are stored at room temperature and 75% relative humidity they absorb moisture rapidly to form the dihydrate (8% water) in about 24 hours.
- the dihydrate continues to absorb water at a slower rate until an equilibrium water content of 13.5% is obtained after 4 days.
- the anhydrate is unstable and hygroscopic.
- the patent publication DD No. 156,532 discloses a process for preparing the ⁇ -form of prazosin hydrochloride by azeotropic distillation of prazosin hydrochloride hydrate in dichlormethane.
- the X-ray diffractogram of the ⁇ -form is characterized by sharp bands at 10.5°, 12.0°, 16.9° and doublets at 24.5° and 26.5°.
- the characteristic bands of the infrared spectrum and the X-ray diffractogram do not differ significantly from the respective characteristic bands of the amorphous anhydrate disclosed in U.S. Pat. No. 4,092,315 (DE No. 2,708,192).
- the ⁇ -form produced by the process of our invention is stable and crystalline, while the anhydrate disclosed in U.S. Pat. No. 4,092,315 (DE No. 2,708,192) is amorphous, unstable and hygroscopic.
- the anhydrous, stable and crystalline ⁇ -form of prazosin hydrochloride is produced by removing the water of crystallization from the dihydrate or polyhydrate prazosin hydrochloride by azeotropic distillation in the presence of selected organic solvents the boiling points of which are in the range of 55°-160° C.
- Preferred selected organic solvents have a boiling point in the range of 70°-110° C. Examples of such selected organic solvents are hexane (b.p. 69° C.), heptane (b.p. 98° C.) and corresponding alkanes with linear or branched chains or cycloalkanes with a higher boiling point.
- Benzene b.p.
- chloroform (b.p. 60° C.), trichlorethylene (b.p. 86° C.), 1,1-dichlorethane (b.p. 58° C.). 1,1,1-trichlorethane (b.p. 72° C.) and corresponding halogenated hydrocarbons having a higher boiling point can be used.
- the ⁇ -form of the prazosin hydrochloride produced by the process of out invention is relatively non-hygroscopic according to the definition of this term in U.S. Pat. No. 4,092,315 (DE No. 2,708,192).
- the moisture content of the ⁇ -form was within the ranges defined for the term "relatively non-hydroscopic" when the ⁇ -form was stored for 30 days in a temperature of 37° C. and a 75% relative humidity.
- the stability of the ⁇ -form of prazosin hydrochloride produced by the process of our invention is also good. Samples were stored for 3 months at 60° C. and the infrared spectra of the samples were compared with the original infrared spectra. No changes cound be found. Samples were also stored at 80° C. and 100° C. without evident changes. The samples were analysed visually and with high pressure liquid chromatography. No visual changes could be observed when the sample was stored for 1 month in daylight.
- the process of our invention is advantageous because of the stable product obtained.
- the solvents used are cheap and easily regenerated. No impurities are produced in the process.
- 1,1,1-trichlorethane 100 g of the dihydrate of prazosin hydrochloride prepared according to the process described in pat. No. DE 3,002,553 was suspended in 1000 ml of 1,1,1-trichlorethane. A water separator was connected to the reaction vessel and the mixture was heated with reflux until water no longer separated (1-2 hours). The precipitate was isolated by filtration and the 1,1,1-trichlorethane was evaporated in reduced pressure. The yield was 93 g (100% of the theorethical) ⁇ -form of prazosin hydrochloride, the infrared spectrum and X-ray diffractogram of which was identical with those disclosed in FIGS. 1 and 2.
- Toluene (b.p. 108° C.) 64 g of undried and washed prazosin hydrochloride taken directly from a watercontaining medium (contains 55% water) was suspended in 750 ml toluene and the mixture was heated under reflux as described in example 1. The yield was 19 g (100% of the theoretical) the ⁇ -form of prazosin hydrochloride.
- the infrared spectrum was identical with the infrared spectrum described in example 1.
- Heptane (b.p. 98° C.) 20 g of the monohydrate of prazosin hydrochloride was suspended in 200 ml of heptane and heated under reflux as described in example 1. The yield was 19 g (100% of the theoretical).
- Chloroform (b.p. 60° C.) 100 g of the dihydrate of prazosin hydrochloride was suspended in 1000 ml of chloroform and heated under reflux as described in example 1. The yield was 84 g (89% of the theoretical).
- 1,2-dichlorethane (b.p. 84° C.). 100 g dihydrate of prazosin hydrochloride was suspended in 1000 ml of 1,2-dichlorethane and the mixture heated under reflux as described in example 1. The yield was 91.5 g (97% of the theoretical).
- Trichlorethylene (b.p. 86° C.) 100 g dihydrate of prazosin hydrochloride was suspended in 1000 ml of trichlorethylene and the mixture was heated under reflux as described in example 1. The yield was 90.5 g (96% of the theoretical).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
TABLE 1 ______________________________________ Characteristic bands cm.sup.-1 μ comments ______________________________________ 1260 7,95 sharp 755 13,3 1005 9,95 triplet ______________________________________
Claims (1)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI842544A FI79107C (en) | 1984-06-25 | 1984-06-25 | Process for the preparation of stable form of prazosin hydrochloride. |
FI842544 | 1984-06-25 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US07/153,780 Division US4873330A (en) | 1984-06-25 | 1988-02-08 | A process for the preparation of anhydrous, stable, crystalline delta-form of prazosin hydrochloride |
Publications (1)
Publication Number | Publication Date |
---|---|
US4739055A true US4739055A (en) | 1988-04-19 |
Family
ID=8519293
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/660,871 Expired - Lifetime US4739055A (en) | 1984-06-25 | 1984-10-15 | Anhydrous, stable, crystalline δ-form of prazosin hydrochloride |
US07/153,780 Expired - Fee Related US4873330A (en) | 1984-06-25 | 1988-02-08 | A process for the preparation of anhydrous, stable, crystalline delta-form of prazosin hydrochloride |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US07/153,780 Expired - Fee Related US4873330A (en) | 1984-06-25 | 1988-02-08 | A process for the preparation of anhydrous, stable, crystalline delta-form of prazosin hydrochloride |
Country Status (17)
Country | Link |
---|---|
US (2) | US4739055A (en) |
JP (1) | JPS6115881A (en) |
AT (1) | AT389117B (en) |
AU (1) | AU566814B2 (en) |
BE (1) | BE900925A (en) |
CH (1) | CH661045A5 (en) |
DE (1) | DE3429415A1 (en) |
FI (1) | FI79107C (en) |
FR (1) | FR2567124B1 (en) |
GB (1) | GB2160861B (en) |
IL (1) | IL73267A (en) |
IT (1) | IT1224142B (en) |
LU (1) | LU85616A1 (en) |
NL (1) | NL8403250A (en) |
NZ (1) | NZ209962A (en) |
PT (1) | PT79411B (en) |
ZA (1) | ZA85910B (en) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE72244T1 (en) * | 1986-03-21 | 1992-02-15 | Heumann Pharma Gmbh & Co | CRYSTALLINE ANHYDROUS SIGMA FORM OF 2-(4-(2FUROYL-(2-PIPERAZINE)-1-YL>-4-AMINO-6,7-DIMETHOXYQUINAZOLINE HYDROCHLORIDE AND PROCESS FOR THEIR PREPARATION. |
JP2756846B2 (en) * | 1989-12-28 | 1998-05-25 | 住化ファインケム株式会社 | Anhydrous ε-type crystal 2- [4- (2-furoyl) piperazin-1-yl] -4-amino-6,7-dimethoxyquinazoline hydrochloride and method for producing the same |
JPH07206857A (en) * | 1993-12-28 | 1995-08-08 | Synthelabo Sa | Alfuzosin hydrochloride dihydrate |
MEP59808A (en) * | 2001-02-24 | 2011-05-10 | Boehringer Ingelheim Pharma | Xanthine derivative, production and use thereof as a medicament |
US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
US7501426B2 (en) * | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
DE102004054054A1 (en) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Process for preparing chiral 8- (3-amino-piperidin-1-yl) -xanthines |
DE102005035891A1 (en) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8- (3-amino-piperidin-1-yl) -xanthines, their preparation and their use as pharmaceuticals |
EP1852108A1 (en) * | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
CA2810839A1 (en) | 2006-05-04 | 2007-11-15 | Boehringer Ingelheim International Gmbh | A polymorphic form of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(r)-amino-piperidin-1-yl)-xanthine |
PE20110235A1 (en) * | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | PHARMACEUTICAL COMBINATIONS INCLUDING LINAGLIPTIN AND METMORPHINE |
CN101784278A (en) * | 2007-08-17 | 2010-07-21 | 贝林格尔.英格海姆国际有限公司 | Purin derivatives for use in the treatment of FAB-related diseases |
PE20140960A1 (en) | 2008-04-03 | 2014-08-15 | Boehringer Ingelheim Int | FORMULATIONS INVOLVING A DPP4 INHIBITOR |
PE20100156A1 (en) * | 2008-06-03 | 2010-02-23 | Boehringer Ingelheim Int | NAFLD TREATMENT |
KR20200118243A (en) | 2008-08-06 | 2020-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | Treatment for diabetes in patients inappropriate for metformin therapy |
UY32030A (en) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "TREATMENT FOR DIABETES IN INAPPROPRIATE PATIENTS FOR THERAPY WITH METFORMIN" |
MX370599B (en) * | 2008-08-15 | 2019-12-18 | Boehringer Ingelheim Int | Purin derivatives for use in the treatment of fab-related diseases. |
US8513264B2 (en) | 2008-09-10 | 2013-08-20 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
AU2009331471B2 (en) | 2008-12-23 | 2015-09-03 | Boehringer Ingelheim International Gmbh | Salt forms of organic compound |
TW201036975A (en) | 2009-01-07 | 2010-10-16 | Boehringer Ingelheim Int | Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy |
KR20240090632A (en) | 2009-11-27 | 2024-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | Treatment of genotyped diabetic patients with dpp-iv inhibitors such as linagliptin |
CN102946875A (en) | 2010-05-05 | 2013-02-27 | 贝林格尔.英格海姆国际有限公司 | Combination therapy |
CA2803504C (en) | 2010-06-24 | 2022-08-30 | Boehringer Ingelheim International Gmbh | A combination for diabetes therapy comprising linagliptin and a long-acting insulin |
US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
DK2731947T3 (en) | 2011-07-15 | 2019-04-23 | Boehringer Ingelheim Int | SUBSTITUTED DIMERIC QUINAZOLINE DERIVATIVE, PREPARATION AND USE thereof IN PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF TYPE I AND TYPE II DIABETES |
US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
EP2849755A1 (en) | 2012-05-14 | 2015-03-25 | Boehringer Ingelheim International GmbH | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
JP6615109B2 (en) | 2014-02-28 | 2019-12-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Medical use of DPP-4 inhibitors |
WO2017211979A1 (en) | 2016-06-10 | 2017-12-14 | Boehringer Ingelheim International Gmbh | Combinations of linagliptin and metformin |
Citations (14)
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---|---|---|---|---|
DE156532C (en) * | ||||
US2194851A (en) * | 1937-05-25 | 1940-03-26 | Melle Usines Sa | Dehydration of organic liquids by azeotropic distillation |
US2969375A (en) * | 1961-01-24 | Certification of correction | ||
US3421983A (en) * | 1967-03-07 | 1969-01-14 | Lummus Co | Azeotropic distillation of aqueous toluene diamine |
US3433788A (en) * | 1966-04-27 | 1969-03-18 | Union Carbide Corp | Process for recovery of amines from aqueous solutions by solvent treatment and distillation |
US3511836A (en) * | 1967-12-13 | 1970-05-12 | Pfizer & Co C | 2,4,6,7-tetra substituted quinazolines |
US3738915A (en) * | 1970-07-01 | 1973-06-12 | Sir Soc Italiana Resine Spa | Method of separating vinyl acetate from liquid mixtures with plural distillations and side stream phase separation |
US3743672A (en) * | 1970-05-27 | 1973-07-03 | Halcon International Inc | Separation of water in alkylene glycol mono and diester purification by azeotropic distillation |
US3857759A (en) * | 1972-06-22 | 1974-12-31 | Montedison Spa | Process for purifying 1,3-dioxolane by treatment with nh{hd 3 {l and distillation with cyclohexane |
US3935213A (en) * | 1973-12-05 | 1976-01-27 | Pfizer Inc. | Process for hypotensive 4-amino-2-(piperazin-1-yl) quinazoline derivatives |
US4001237A (en) * | 1976-02-18 | 1977-01-04 | Bristol-Myers Company | Oxazole, isoxazole, thiazole and isothiazole amides |
US4026894A (en) * | 1975-10-14 | 1977-05-31 | Abbott Laboratories | Antihypertensive agents |
US4092315A (en) * | 1976-03-01 | 1978-05-30 | Pfizer Inc. | Novel crystalline forms of prazosin hydrochloride |
US4271300A (en) * | 1979-01-31 | 1981-06-02 | Orion-Yhtyma Oy | Method for producing 6,7-dimethoxy-4-amino-2-[4-(2-furoyl)-1-piperazinyl] qu |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1156973A (en) * | 1965-07-06 | 1969-07-02 | Quinazoline Derivatives | |
FI64367C (en) * | 1980-02-26 | 1986-08-05 | Orion Yhtymae Oy | OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE |
-
1984
- 1984-06-25 FI FI842544A patent/FI79107C/en not_active IP Right Cessation
- 1984-08-09 DE DE19843429415 patent/DE3429415A1/en active Granted
- 1984-10-03 GB GB08424999A patent/GB2160861B/en not_active Expired
- 1984-10-15 US US06/660,871 patent/US4739055A/en not_active Expired - Lifetime
- 1984-10-19 IL IL73267A patent/IL73267A/en not_active IP Right Cessation
- 1984-10-19 AU AU34510/84A patent/AU566814B2/en not_active Ceased
- 1984-10-23 NZ NZ209962A patent/NZ209962A/en unknown
- 1984-10-24 IT IT23292/84A patent/IT1224142B/en active
- 1984-10-25 NL NL8403250A patent/NL8403250A/en not_active Application Discontinuation
- 1984-10-26 FR FR8416401A patent/FR2567124B1/en not_active Expired - Fee Related
- 1984-10-26 CH CH5142/84A patent/CH661045A5/en not_active IP Right Cessation
- 1984-10-26 PT PT79411A patent/PT79411B/en not_active IP Right Cessation
- 1984-10-29 LU LU85616A patent/LU85616A1/en unknown
- 1984-10-29 JP JP59227640A patent/JPS6115881A/en active Granted
- 1984-10-29 BE BE0/213911A patent/BE900925A/en not_active IP Right Cessation
- 1984-10-30 AT AT0344184A patent/AT389117B/en not_active IP Right Cessation
-
1985
- 1985-02-06 ZA ZA85910A patent/ZA85910B/en unknown
-
1988
- 1988-02-08 US US07/153,780 patent/US4873330A/en not_active Expired - Fee Related
Patent Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2969375A (en) * | 1961-01-24 | Certification of correction | ||
DE156532C (en) * | ||||
US2194851A (en) * | 1937-05-25 | 1940-03-26 | Melle Usines Sa | Dehydration of organic liquids by azeotropic distillation |
US3433788A (en) * | 1966-04-27 | 1969-03-18 | Union Carbide Corp | Process for recovery of amines from aqueous solutions by solvent treatment and distillation |
US3421983A (en) * | 1967-03-07 | 1969-01-14 | Lummus Co | Azeotropic distillation of aqueous toluene diamine |
US3511836A (en) * | 1967-12-13 | 1970-05-12 | Pfizer & Co C | 2,4,6,7-tetra substituted quinazolines |
US3743672A (en) * | 1970-05-27 | 1973-07-03 | Halcon International Inc | Separation of water in alkylene glycol mono and diester purification by azeotropic distillation |
US3738915A (en) * | 1970-07-01 | 1973-06-12 | Sir Soc Italiana Resine Spa | Method of separating vinyl acetate from liquid mixtures with plural distillations and side stream phase separation |
US3857759A (en) * | 1972-06-22 | 1974-12-31 | Montedison Spa | Process for purifying 1,3-dioxolane by treatment with nh{hd 3 {l and distillation with cyclohexane |
US3935213A (en) * | 1973-12-05 | 1976-01-27 | Pfizer Inc. | Process for hypotensive 4-amino-2-(piperazin-1-yl) quinazoline derivatives |
US4026894A (en) * | 1975-10-14 | 1977-05-31 | Abbott Laboratories | Antihypertensive agents |
US4001237A (en) * | 1976-02-18 | 1977-01-04 | Bristol-Myers Company | Oxazole, isoxazole, thiazole and isothiazole amides |
US4092315A (en) * | 1976-03-01 | 1978-05-30 | Pfizer Inc. | Novel crystalline forms of prazosin hydrochloride |
US4271300A (en) * | 1979-01-31 | 1981-06-02 | Orion-Yhtyma Oy | Method for producing 6,7-dimethoxy-4-amino-2-[4-(2-furoyl)-1-piperazinyl] qu |
Non-Patent Citations (2)
Title |
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Perry, Chemical Engineers Handbook, 4th Ed., McGraw Hill, New York, pp. 13 49 to 13 51. * |
Perry, Chemical Engineers' Handbook, 4th Ed., McGraw-Hill, New York, pp. 13-49 to 13-51. |
Also Published As
Publication number | Publication date |
---|---|
CH661045A5 (en) | 1987-06-30 |
BE900925A (en) | 1985-02-15 |
AU566814B2 (en) | 1987-10-29 |
PT79411A (en) | 1984-11-01 |
GB8424999D0 (en) | 1984-11-07 |
LU85616A1 (en) | 1985-06-04 |
GB2160861B (en) | 1987-11-18 |
FI79107C (en) | 1989-11-10 |
FI842544A (en) | 1985-12-26 |
IT8423292A0 (en) | 1984-10-24 |
DE3429415C2 (en) | 1990-05-03 |
IL73267A0 (en) | 1985-01-31 |
PT79411B (en) | 1986-09-15 |
AU3451084A (en) | 1986-01-02 |
FR2567124A1 (en) | 1986-01-10 |
AT389117B (en) | 1989-10-25 |
FI79107B (en) | 1989-07-31 |
IT1224142B (en) | 1990-09-26 |
FR2567124B1 (en) | 1990-09-21 |
FI842544A0 (en) | 1984-06-25 |
IL73267A (en) | 1988-06-30 |
NL8403250A (en) | 1986-01-16 |
JPH0481993B2 (en) | 1992-12-25 |
ATA344184A (en) | 1989-03-15 |
DE3429415A1 (en) | 1986-01-02 |
GB2160861A (en) | 1986-01-02 |
ZA85910B (en) | 1985-09-25 |
NZ209962A (en) | 1987-06-30 |
JPS6115881A (en) | 1986-01-23 |
US4873330A (en) | 1989-10-10 |
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